A lactam is a cyclic amide, formally derived from an amino alkanoic acid through cyclization reactions. The term is a portmanteau of the words lactone + amide .
A lactam is a cyclic amide, formally derived from an amino alkanoic acid through cyclization reactions. The term is a portmanteau of the words lactone + amide .
Greek prefixes in alphabetical order indicate ring size.
| Ring size (number of atoms in the ring) | Systematic name | IUPAC name | Common name (s) | Structure |
|---|---|---|---|---|
| 3 | α-Lactam | Aziridin-2-one | α-Acetolactam |  |
| 4 | β-Lactam | Azetidin-2-one | β-Propiolactam |  |
| 5 | γ-Lactam | Pyrrolidin-2-one |
|  |
| 6 | δ-Lactam | Piperidin-2-one |
|  |
| 7 | ε-Lactam | Azepan-2-one |
|  |
This ring-size nomenclature stems from the fact that hydrolysis of an α-lactam gives an α-amino acid and that of a β-Lactam gives a β-amino acid, and so on.
General synthetic methods are used for the organic synthesis of lactams.
Lactams form by the acid-catalyzed rearrangement of oximes in the Beckmann rearrangement.
Lactams form from cyclic ketones and hydrazoic acid in the Schmidt reaction. Cyclohexanone with hydrazoic acid, forms ε - Caprolactum, which upon treatment with excess acid forms Cardiazole, a heart stimulant.
Lactams can be formed from cyclisation of amino acids via the coupling between an amine and a carboxylic acid within the same molecule. Lactamization is most efficient in this way if the product is a γ-lactam. For example, Fmoc-Dab(Mtt)-OH, although its side-chain amine is sterically protected by extremely bulky 4-Methyltrityl (Mtt) group, the amine can still intramolecularly couple with the carboxylic acid to form a γ-lactam. This reaction almost finished within 5 minutes with many coupling reagents (e.g. HATU and PyAOP). [1]
Lactams form from intramolecular attack of linear acyl derivatives from the nucleophilic abstraction reaction.
An iminium ion reacts with a halonium ion formed in situ by reaction of an alkene with iodine. [2]
Lactams form by copper-catalyzed 1,3-dipolar cycloaddition of alkynes and nitrones in the Kinugasa reaction
Diels-Alder reaction between cyclopentadiene and chlorosulfonyl isocyanate (CSI) can be utilized to obtain both β- as well as γ-lactam. At lower temp (−78 °C), β-lactam is the preferred product. At optimum temperatures, a highly useful γ-lactam known as Vince Lactam [3] is obtained. [4]
A lactim is a cyclic imidic acid compound characterized by an endocyclic carbon-nitrogen double bond. They are formed when lactams undergo tautomerization.
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula R−C(=O)−NR′R″, where R, R', and R″ represent any group, typically organyl groups or hydrogen atoms. The amide group is called a peptide bond when it is part of the main chain of a protein, and an isopeptide bond when it occurs in a side chain, as in asparagine and glutamine. It can be viewed as a derivative of a carboxylic acid with the hydroxyl group replaced by an amine group ; or, equivalently, an acyl (alkanoyl) group joined to an amine group.
In chemistry, an ester is a compound derived from an acid in which the hydrogen atom (H) of at least one acidic hydroxyl group of that acid is replaced by an organyl group. These compounds contain a distinctive functional group. Analogues derived from oxygen replaced by other chalcogens belong to the ester category as well. According to some authors, organyl derivatives of acidic hydrogen of other acids are esters as well, but not according to the IUPAC.
In organic chemistry, a ketene is an organic compound of the form RR'C=C=O, where R and R' are two arbitrary monovalent chemical groups. The name may also refer to the specific compound ethenone H2C=C=O, the simplest ketene.
Lactones are cyclic carboxylic esters. They are derived from the corresponding hydroxycarboxylic acids by esterification. They can be saturated or unsaturated.
A polyamide is a polymer with repeating units linked by amide bonds.
In organic chemistry, an imine is a functional group or organic compound containing a carbon–nitrogen double bond. The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bonds. Imines are common in synthetic and naturally occurring compounds and they participate in many reactions.
A dipeptide is an organic compound derived from two amino acids. The constituent amino acids can be the same or different. When different, two isomers of the dipeptide are possible, depending on the sequence. Several dipeptides are physiologically important, and some are both physiologically and commercially significant. A well known dipeptide is aspartame, an artificial sweetener.
In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxyl group of one amino acid to the amino group of another. Protecting group strategies are usually necessary to prevent undesirable side reactions with the various amino acid side chains. Chemical peptide synthesis most commonly starts at the carboxyl end of the peptide (C-terminus), and proceeds toward the amino-terminus (N-terminus). Protein biosynthesis in living organisms occurs in the opposite direction.
In organic chemistry, the Ugi reaction is a multi-component reaction involving a ketone or aldehyde, an amine, an isocyanide and a carboxylic acid to form a bis-amide. The reaction is named after Ivar Karl Ugi, who first reported this reaction in 1959.
The Claisen rearrangement is a powerful carbon–carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen. The heating of an allyl vinyl ether will initiate a [3,3]-sigmatropic rearrangement to give a γ,δ-unsaturated carbonyl, driven by exergonically favored carbonyl CO bond formation Δ(ΔfH) = −327 kcal/mol (−1,370 kJ/mol).
The Curtius rearrangement, first defined by Theodor Curtius in 1885, is the thermal decomposition of an acyl azide to an isocyanate with loss of nitrogen gas. The isocyanate then undergoes attack by a variety of nucleophiles such as water, alcohols and amines, to yield a primary amine, carbamate or urea derivative respectively. Several reviews have been published.
The Weinreb ketone synthesis or Weinreb–Nahm ketone synthesis is a chemical reaction used in organic chemistry to make carbon–carbon bonds. It was discovered in 1981 by Steven M. Weinreb and Steven Nahm as a method to synthesize ketones. The original reaction involved two subsequent substitutions: the conversion of an acid chloride with N,O-Dimethylhydroxylamine, to form a Weinreb–Nahm amide, and subsequent treatment of this species with an organometallic reagent such as a Grignard reagent or organolithium reagent. Nahm and Weinreb also reported the synthesis of aldehydes by reduction of the amide with an excess of lithium aluminum hydride.
The Petasis reaction is the multi-component reaction of an amine, a carbonyl, and a vinyl- or aryl-boronic acid to form substituted amines.
The Wolff rearrangement is a reaction in organic chemistry in which an α-diazocarbonyl compound is converted into a ketene by loss of dinitrogen with accompanying 1,2-rearrangement. The Wolff rearrangement yields a ketene as an intermediate product, which can undergo nucleophilic attack with weakly acidic nucleophiles such as water, alcohols, and amines, to generate carboxylic acid derivatives or undergo [2+2] cycloaddition reactions to form four-membered rings. The mechanism of the Wolff rearrangement has been the subject of debate since its first use. No single mechanism sufficiently describes the reaction, and there are often competing concerted and carbene-mediated pathways; for simplicity, only the textbook, concerted mechanism is shown below. The reaction was discovered by Ludwig Wolff in 1902. The Wolff rearrangement has great synthetic utility due to the accessibility of α-diazocarbonyl compounds, variety of reactions from the ketene intermediate, and stereochemical retention of the migrating group. However, the Wolff rearrangement has limitations due to the highly reactive nature of α-diazocarbonyl compounds, which can undergo a variety of competing reactions.
The Kulinkovich reaction describes the organic synthesis of substituted cyclopropanols through reaction of esters with dialkyldialkoxytitanium reagents, which are generated in situ from Grignard reagents containing a hydrogen in beta-position and titanium(IV) alkoxides such as titanium isopropoxide. This reaction was first reported by Oleg Kulinkovich and coworkers in 1989.
In organic chemistry, the Schmidt reaction is an organic reaction in which an azide reacts with a carbonyl derivative, usually an aldehyde, ketone, or carboxylic acid, under acidic conditions to give an amine or amide, with expulsion of nitrogen. It is named after Karl Friedrich Schmidt (1887–1971), who first reported it in 1924 by successfully converting benzophenone and hydrazoic acid to benzanilide. The intramolecular reaction was not reported until 1991 but has become important in the synthesis of natural products. The reaction is effective with carboxylic acids to give amines (above), and with ketones to give amides (below).
The Hofmann–Löffler reaction (also referred to as Hofmann–Löffler–Freytag reaction, Löffler–Freytag reaction, Löffler–Hofmann reaction, as well as Löffler's method) is an organic reaction in which a cyclic amine 2 (pyrrolidine or, in some cases, piperidine) is generated by thermal or photochemical decomposition of N-halogenated amine 1 in the presence of a strong acid (concentrated sulfuric acid or concentrated CF3CO2H). The Hofmann–Löffler–Freytag reaction proceeds via an intramolecular hydrogen atom transfer to a nitrogen-centered radical and is an example of a remote intramolecular free radical C–H functionalization.
The Staudinger synthesis, also called the Staudinger ketene-imine cycloaddition, is a chemical synthesis in which an imine 1 reacts with a ketene 2 through a non-photochemical 2+2 cycloaddition to produce a β-lactam3. The reaction carries particular importance in the synthesis of β-lactam antibiotics. The Staudinger synthesis should not be confused with the Staudinger reaction, a phosphine or phosphite reaction used to reduce azides to amines.
Shiina macrolactonization is an organic chemical reaction that synthesizes cyclic compounds by using aromatic carboxylic acid anhydrides as dehydration condensation agents. In 1994, Prof. Isamu Shiina reported an acidic cyclization method using Lewis acid catalyst, and, in 2002, a basic cyclization using nucleophilic catalyst.
Thomas Lectka is an American organic chemist, academic and researcher. He is Jean and Norman Scowe Professor of Chemistry and leads the Lectka Group at Johns Hopkins University.
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